Epstein-Barr virus (EBV) is a virus widely distributed in the world, belonging to the family Herpes, the subfamily Gammaherpes, and the genus Lyphocryptovirus. Once infected with EBV, EBV entering a genome of a B lymphocyte is not eliminated by an immune response. Accordingly, the B lymophocyte may be maintained in latent infection. In regard to the age associated with primary EBV infection depending on hygienic environments, about 80%, about 90%, and about 100% of positive rates are shown in 3-year-olds, about 20-years-old, and late 20s, respectively. The primary infection in childhood may cause asymptomatic or mild symptoms. However, the primary injection in adolescence may cause infectious mononucleosis (IM) in some cases, or chronic EBV infection in other cases. In addition, in a re-activation process of EBV having latent infection, opportunistic B cell lymphoma, Burkitt's lymphoma (BL), or nasopharyngeal carcinoma (NPC) may be caused. It is not well known why the disease incidence is different depending on the primary infection ages, but it is assumed that such difference may exist depending on maturity of a biological immune mechanism. EBV is an important carcinogen that causes many neoplastic disorders, and cells for lytic infection stimulate the growth of EBV-associated malignant tumors. Such phenomenon above may be related to an increase in angiogenesis EBV infection is rare in eye retina, but in the actual clinical practice, EBV-associated retinitis have been reported as one of complications of chronic active EBV infection. It is known that angiogenesis accompanies subsequent retinal necrosis.
Angiogenesis is a phenomenon of forming new blood vessels from existing blood vessels. It has known that angiogenesis is highly involved in crisis or development of diseases, such as malignant (solid) neoplasm, diabetic retiniopathy, senile macular degeneration, and inflammatory disease, e.g., rheumatoid arthritis. In addition, in consideration of metastasis that has become a major problem on cancer treatment, angiogenesis is an important step in terms of ensuring a path of metastasis. As such, angiogenesis is observed in a variety of lesions and may promote progress in each of the conditions. Thus, it is urgent to development a model applicable to evaluate angiogenesis and drug efficacy during the development of various drugs. In particular, the development of cell models has advantages of consuming a significantly lower cost compared with a cost required for clinical models and models for animal tests, and obtaining results by easy treatment, thereby having significantly high effectiveness.
Meanwhile, the Korean Patent No. 10-2008-0009530 (published on Jan. 30, 2008) discloses a method for screening an angiogenesis inhibitor, the method including screening an angiogenesis inhibitor through a contact between ubiquinone-binding protein (QP-C) of mitochondrial complex III and a test material. However, there is no reference to the cell model for diseases associated with corneal neovascularization using EBV-infected HIECs of the present invention.
Therefore, the present inventors have completed the present invention by indicating that the EBV-infected HCECs have a cell shape in a spindle form, are elongated, and show fibroblast-like characteristics and by confirming that expression of factors that are known to be involved in angiogenesis is relatively increased.